Dr. Christian is an Assistant Professor in the Department of Cell and Developmental Biology. Her research program focusses on the embryonic roles of Wnt proteins in Xenopus laevis. In the project described in this proposal, she is studying the functions of two Wnt-related genes, Xwnt-8 and Xwnt-8b, in neural and mesodermal patterning. Xwnt-8 is normally expressed in presumtive ventral mesoderm. When Xwnt-8 is ectopically expressed in the dorsal mesoderm, these cells are respecified with a more ventral fate and embryos exhibit a loss of the forebrain. The initial goal of this project is to determine how misexpression of Xwnt-8 in the mesoderm perturbs pattern in the central nervous system. Two hypotheses will he tested: that misexpressed Xwnt-8 masks anterior inductive signals by retarding the involution of the dorsal mesoderm, or that it leads to a loss of mesodermally derived anterior inducing signals. A second objective is to use a subtractive hybridization approach to identify molecules that are expressed in response to, and might function downstream of, Xwnt-8 in ventral patterning. Finally, to begin functional analysis of a related Wnt, Xwnt-8b, and to examine structure/function relationships of Wnt proteins, the following aims will be completed: 1. A full length cDNA encoding Xwnt-8b will be isolated. 2. Normal expression of Xwnt-8b will be upregulated and downregulated in Xenopus embryos using ectopic expression and antisense approaches, respectively. Effects on cell fate and tissue pattern will be assessed. 3. Functional domains of Xwnt-8 and Xwnt-8b will be identified by assaying the biological activity of deletion mutant and chimeric Xwnt-8/Xwnt-8b proteins. Collectively these studies will contribute to an understanding of cellular and molecular mechanisms by which these, and possibly all, Wnts generate pattern during normal vertebrate development. Dr. Christian's responsibilities now involve teaching medical and graduate students in five different courses, as well as departmental administrative responsibilities. The award of an RCDA would relieve Dr. Christian of her substantial medical school teaching load, enabling her to devote more time to research at this crucial point in her career. In particular, it would allow her to dedicate sufficient time to her new project on post-transcriptional regulation of Wnt gene expression to develop this into an independently funded line of research. OHSU has a strong, highly collaborative research program that encourages interactions among departments.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02HD001167-02
Application #
2634871
Study Section
Maternal and Child Health Research Committee (HDMC)
Project Start
1997-01-01
Project End
2001-12-31
Budget Start
1998-01-01
Budget End
1998-12-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239
Tian, Qi; Jin, Hong; Cui, Yanzhen et al. (2005) Regulation of Wnt gene expression. Dev Growth Differ 47:273-81
Walters, Melinda J; Wayman, Gary A; Notis, John C et al. (2002) Calmodulin-dependent protein kinase IV mediated antagonism of BMP signaling regulates lineage and survival of hematopoietic progenitors. Development 129:1455-66
Walters, M J; Wayman, G A; Christian, J L (2001) Bone morphogenetic protein function is required for terminal differentiation of the heart but not for early expression of cardiac marker genes. Mech Dev 100:263-73
Nakayama, T; Berg, L K; Christian, J L (2001) Dissection of inhibitory Smad proteins: both N- and C-terminal domains are necessary for full activities of Xenopus Smad6 and Smad7. Mech Dev 100:251-62
Wayman, G A; Walters, M J; Kolibaba, K et al. (2000) CaM kinase IV regulates lineage commitment and survival of erythroid progenitors in a non-cell-autonomous manner. J Cell Biol 151:811-24
Tian, Q; Nakayama, T; Dixon, M P et al. (1999) Post-transcriptional regulation of Xwnt-8 expression is required for normal myogenesis during vertebrate embryonic development. Development 126:3371-80
Nakayama, T; Snyder, M A; Grewal, S S et al. (1998) Xenopus Smad8 acts downstream of BMP-4 to modulate its activity during vertebrate embryonic patterning. Development 125:857-67
Nakayama, T; Gardner, H; Berg, L K et al. (1998) Smad6 functions as an intracellular antagonist of some TGF-beta family members during Xenopus embryogenesis. Genes Cells 3:387-94
Cui, Y; Jean, F; Thomas, G et al. (1998) BMP-4 is proteolytically activated by furin and/or PC6 during vertebrate embryonic development. EMBO J 17:4735-43